Diabetes mellitus is a highly significant health problem, affecting more than 25 million people in the United States alone. Our understanding of the pathogenesis of diabetes has benefited immensely from the molecular genetic analysis of the disease both in human and in rodent models. Advances in genomics technologies have enabled investigators in the fields of diabetes and endocrinology to simultaneously analyze the expression levels of thousands of genes, and analyze their epigenetic regulation. During the past grant cycle, we have dramatically expanded the capabilities of our well-utilized Functional Genomics Core to serve the DRC's membership needs. We have acquired four next generation sequencing instruments and established multiple applications, including ChIP-Seq for transcription factor occupancy and histone modifications, exome capture and sequencing, RNA-Seq, microRNA-Seq, HITS-CLIP, ATAC-Seq, and methylome analysis. During the next grant cycle, we will offer an expanded repertoire of next generation sequencing services, including library construction and bioinformatics analysis to the DRC's membership. We have recruited Dr. K.-J. Won, an expert computational biologist, to provide advanced bioinformatics analysis exclusively for DRC members. The Core will interact closely with the other DRC cores, for instance in correlating the phenotypic analysis performed on genetically altered or metabolically challenged mice with their expression profiles, including single cell RNAseq, and epigenetic regulation to greatly enhance the power of each individual analysis. Furthermore, similar assessments of the function of control and diabetic human islets from the same donor by the islet biology and functional genomics core will provide valuable functional information that may be integrated with changes in DNA sequence or genome-wide measurements of epigenetic regulation or gene expression. This core, in conjunction with the others, will help measure and understand the normal and pathologic genetic and epigenetic states of islets, adipose tissue, liver, and other important tissues types as it relates to the development and function of these tissues.